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Vaccines in development against West Nile virus.

Brandler S, Tangy F - Viruses (2013)

Bottom Line: In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine.MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines.A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génomique Virale et Vaccination, INSTITUT PASTEUR, 28 rue du Dr Roux, Paris 75015, France. samantha.brandler@pasteur.fr.

ABSTRACT
West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

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West Nile virus (WNV) challenge of squirrel monkeys immunized with MVSchw-sEWNV. Twelve monkeys immunized with MVSchw-sEWNV and four monkeys mock immunized (with empty MV vaccine) or phosphate-buffered saline (PBS)) were challenged with WNV IS-98-ST1, either 15 or 30 days after immunization. (A) and (B): WNV-specific antibody levels were determined by enzyme-linked immunosorbent assay on the day of immunization, 15 days after immunization, the day of challenge, seven days after challenge and on the day of euthanasia. (C) The presence of WNV genomic RNA was determined by quantitative real-time polymerase chain reaction on day 2 after challenge in the serum of challenged animals. Animals 3, 4, 5 and 6 received one vaccination on day 30 before challenge; animals 9, 10, 11 and 12 received one vaccination on day 15 before challenge; and animals 1 and 2 (PBS) and 7 and 8 (MV) were mock infected. (D) The mean WNV titer in the serum of vaccinated animals, determined by the plaque formation assay at day 2 after challenge. Abbreviations: OD, optical density; pfu, plaque-forming units.
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viruses-05-02384-f003: West Nile virus (WNV) challenge of squirrel monkeys immunized with MVSchw-sEWNV. Twelve monkeys immunized with MVSchw-sEWNV and four monkeys mock immunized (with empty MV vaccine) or phosphate-buffered saline (PBS)) were challenged with WNV IS-98-ST1, either 15 or 30 days after immunization. (A) and (B): WNV-specific antibody levels were determined by enzyme-linked immunosorbent assay on the day of immunization, 15 days after immunization, the day of challenge, seven days after challenge and on the day of euthanasia. (C) The presence of WNV genomic RNA was determined by quantitative real-time polymerase chain reaction on day 2 after challenge in the serum of challenged animals. Animals 3, 4, 5 and 6 received one vaccination on day 30 before challenge; animals 9, 10, 11 and 12 received one vaccination on day 15 before challenge; and animals 1 and 2 (PBS) and 7 and 8 (MV) were mock infected. (D) The mean WNV titer in the serum of vaccinated animals, determined by the plaque formation assay at day 2 after challenge. Abbreviations: OD, optical density; pfu, plaque-forming units.

Mentions: We used this model to evaluate the immunogenicity and protective efficacy of MVSchw-sEWNV vaccine candidate. Squirrel monkeys were immunized intramuscularly with a single dose of 3.0 × 106 tissue culture infective dose (TCID50) of vaccine and then challenged intravenously 15 or 30 days later with 105 pfu of WNV IS98-ST1. No vaccine-associated adverse effects were observed, and as early as 15 days after immunization, WNV-specific IgG were detectable in six of eight animals. Additionally, ELISA titers increased sharply by day 30 post-immunization (Figure 3A,B). Neutralizing antibodies were also detected at day 15 and 30. At challenge, a slight increase in body temperature was recorded in control animals that received either or phosphate-buffered saline (PBS) or empty MV virus, but not in MVSchw-sEWNV vaccinated animals. IgG antibodies titers in animals challenged 30 days post-immunization remained high and unchanged, while they were boosted in animals challenged 15 days post-immunization. In all vaccinated animals, the post-challenge neutralizing titers was one log higher than in control animals, indicating a boost of vaccine memory during WNV infection. A strong reduction of viremia was observed in both groups challenged 30 or 15 days after immunization (Figure 3C,D). In animals challenged 30 days after immunization, a three log reduction (99.8%) of WNV RNA copy number in plasma was observed, with no infectious titer detectable, whereas in the animals challenged only 15 days after immunization, a significant 10-fold reduction (85%) was still observed. Due to BSL4 constraints, long-term studies were not performed, but our previous studies demonstrate that the recombinant MV vector induces a long-term immune response.


Vaccines in development against West Nile virus.

Brandler S, Tangy F - Viruses (2013)

West Nile virus (WNV) challenge of squirrel monkeys immunized with MVSchw-sEWNV. Twelve monkeys immunized with MVSchw-sEWNV and four monkeys mock immunized (with empty MV vaccine) or phosphate-buffered saline (PBS)) were challenged with WNV IS-98-ST1, either 15 or 30 days after immunization. (A) and (B): WNV-specific antibody levels were determined by enzyme-linked immunosorbent assay on the day of immunization, 15 days after immunization, the day of challenge, seven days after challenge and on the day of euthanasia. (C) The presence of WNV genomic RNA was determined by quantitative real-time polymerase chain reaction on day 2 after challenge in the serum of challenged animals. Animals 3, 4, 5 and 6 received one vaccination on day 30 before challenge; animals 9, 10, 11 and 12 received one vaccination on day 15 before challenge; and animals 1 and 2 (PBS) and 7 and 8 (MV) were mock infected. (D) The mean WNV titer in the serum of vaccinated animals, determined by the plaque formation assay at day 2 after challenge. Abbreviations: OD, optical density; pfu, plaque-forming units.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814594&req=5

viruses-05-02384-f003: West Nile virus (WNV) challenge of squirrel monkeys immunized with MVSchw-sEWNV. Twelve monkeys immunized with MVSchw-sEWNV and four monkeys mock immunized (with empty MV vaccine) or phosphate-buffered saline (PBS)) were challenged with WNV IS-98-ST1, either 15 or 30 days after immunization. (A) and (B): WNV-specific antibody levels were determined by enzyme-linked immunosorbent assay on the day of immunization, 15 days after immunization, the day of challenge, seven days after challenge and on the day of euthanasia. (C) The presence of WNV genomic RNA was determined by quantitative real-time polymerase chain reaction on day 2 after challenge in the serum of challenged animals. Animals 3, 4, 5 and 6 received one vaccination on day 30 before challenge; animals 9, 10, 11 and 12 received one vaccination on day 15 before challenge; and animals 1 and 2 (PBS) and 7 and 8 (MV) were mock infected. (D) The mean WNV titer in the serum of vaccinated animals, determined by the plaque formation assay at day 2 after challenge. Abbreviations: OD, optical density; pfu, plaque-forming units.
Mentions: We used this model to evaluate the immunogenicity and protective efficacy of MVSchw-sEWNV vaccine candidate. Squirrel monkeys were immunized intramuscularly with a single dose of 3.0 × 106 tissue culture infective dose (TCID50) of vaccine and then challenged intravenously 15 or 30 days later with 105 pfu of WNV IS98-ST1. No vaccine-associated adverse effects were observed, and as early as 15 days after immunization, WNV-specific IgG were detectable in six of eight animals. Additionally, ELISA titers increased sharply by day 30 post-immunization (Figure 3A,B). Neutralizing antibodies were also detected at day 15 and 30. At challenge, a slight increase in body temperature was recorded in control animals that received either or phosphate-buffered saline (PBS) or empty MV virus, but not in MVSchw-sEWNV vaccinated animals. IgG antibodies titers in animals challenged 30 days post-immunization remained high and unchanged, while they were boosted in animals challenged 15 days post-immunization. In all vaccinated animals, the post-challenge neutralizing titers was one log higher than in control animals, indicating a boost of vaccine memory during WNV infection. A strong reduction of viremia was observed in both groups challenged 30 or 15 days after immunization (Figure 3C,D). In animals challenged 30 days after immunization, a three log reduction (99.8%) of WNV RNA copy number in plasma was observed, with no infectious titer detectable, whereas in the animals challenged only 15 days after immunization, a significant 10-fold reduction (85%) was still observed. Due to BSL4 constraints, long-term studies were not performed, but our previous studies demonstrate that the recombinant MV vector induces a long-term immune response.

Bottom Line: In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine.MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines.A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génomique Virale et Vaccination, INSTITUT PASTEUR, 28 rue du Dr Roux, Paris 75015, France. samantha.brandler@pasteur.fr.

ABSTRACT
West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

Show MeSH
Related in: MedlinePlus